Description: (Applicant's Description) The Breast Cancer Program is integrated and comprehensive spanning basic, translational and clinical research. One area of basic research is focused on understanding the biology of the MCF10AT model of human preneoplastic, proliferative breast disease, which was developed by members of this Program. This xenograft model recapitulates the histological stigmata of early breast cancer development: atypical hyperplasia (AH), carcinoma in situ (CIS) with progression to invasive cancer. Estrogen enhances, and tamoxifen inhibits, both AH and CIS. Translational research utilizes this model as a preclinical test system of prevention agents and strategies. This work is part of an interprogrammatic collaboration with the Molecular Biology and Genetics and the Population Studies and Prevention Programs, ultimately aimed at testing prevention approaches in the community-research setting. Current emphasis is on control of breast cancer risk by dietary modification and chemoprevention. A second area of basic research is steroid and peptide signaling factors and receptors in breast cancer growth and development and the interface of these factors/receptors with each other and in epithelial-stromal interactions. Translational/clinical research efforts are also directed towards development of more efficacious therapy for breast cancer patients. Goals include development of effective biological/immunological based therapy, elucidation of the parameters that lead to a favorable outcome of high dose chemotherapy with autologous stem cell transplantation, and integration of biological therapy into the high dose setting. Basic/translational research in these areas is focused on vaccine development, on in vitro immunization for adoptive immunotherapy and on mechanisms of treatment failure. These studies form the foundation of ongoing and planned clinical trials.